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Biomedical subjects

X G Sun

Publications and source records attributed to X G Sun.

18 recordsLinked to original sources

Exercise pathophysiology in patients with primary pulmonary hypertension.

BACKGROUND: Patients with primary pulmonary hypertension (PPH) have a pulmonary vasculopathy that leads to exercise intolerance due to dyspnea and fatigue. To better understand the basis of the exercise limitation in patients with PPH, cardiopulmonary exercise testing (CPET) with gas exchange measurements, New York Heart Association (NYHA) symptom class, and resting pulmonary hemodynamics were studied. METHODS AND RESULTS: We retrospectively evaluated 53 PPH patients who had right heart catheterization and cycle ergometer CPET studies to maximum tolerance as part of their clinical workups. No adverse events occurred during CPET. Reductions in peak O(2) uptake (VO(2)), anaerobic threshold, peak O(2) pulse, rate of increase in VO(2), and ventilatory efficiency were consistently found. NYHA class correlated well with the above parameters of aerobic function and ventilatory efficiency but less well with resting pulmonary hemodynamics. CONCLUSIONS: Patients with PPH can safely undergo noninvasive cycle ergometer CPET to their maximal tolerance. The CPET abnormalities were consistent and characteristic and correlated well with NYHA class.

Adult↗

Differential expression of adenylyl cyclases in the rat nephron.

BACKGROUND: Adenylyl cyclases (ACs) are a family of enzymes that catalyze the formation of the second-messenger cyclic adenosine 3',5'-monophosphate (cAMP). At least nine isoforms of AC have been cloned. These isoforms differ in their tissue distribution and basal activity. AC isoforms also differ in their capacity to be stimulated or inhibited by G protein alpha(i), alpha(s) and beta/gamma subunits, protein kinase C, and intracellular calcium. The distribution of ACs in the kidney is only partially known, although it is known that ACs play important roles in kidney signal transduction. Several receptors are known to couple to AC, but their linkage to individual AC isoforms in the kidney is not known. METHODS: This study investigated the tissue distribution of AC isoforms along the nephron of Wistar-Kyoto rats using reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and immunoblotting. RESULTS: While AC VI and IX mRNA were found in all nephron segments, there was no expression of AC VIII mRNA. ACs II through V and VII mRNA were variably found in specific nephron segments. mRNA for AC isoforms II, III, VI, VII, and IX were expressed in renal proximal tubules. All of the AC isoforms studied, except VIII, were found in glomeruli. Immunoblotting and immunohistochemistry confirmed the mRNA results. AC isoforms II, III, IV, and IX were expressed in luminal rather than in basolateral membranes. However, immunohistochemical studies were not feasible for the other isoforms that could be expressed in basolateral membranes. CONCLUSION: Knowledge of the distribution of ACs may help establish the linkage between receptors and specific AC isoforms and define their functions.

Adenylyl Cyclases↗

Carbon dioxide pressure-concentration relationship in arterial and mixed venous blood during exercise.

To calculate cardiac output by the indirect Fick principle, CO(2) concentrations (CCO(2)) of mixed venous (Cv(CO(2))) and arterial blood are commonly estimated from PCO(2), based on the assumption that the CO(2) pressure-concentration relationship (PCO(2)-CCO(2)) is influenced more by changes in Hb concentration and blood oxyhemoglobin saturation than by changes in pH. The purpose of the study was to measure and assess the relative importance of these variables, both in arterial and mixed venous blood, during rest and increasing levels of exercise to maximum (Max) in five healthy men. Although the mean mixed venous PCO(2) rose from 47 Torr at rest to 59 Torr at the lactic acidosis threshold (LAT) and further to 78 Torr at Max, the Cv(CO(2)) rose from 22.8 mM at rest to 25.5 mM at LAT but then fell to 23.9 mM at Max. Meanwhile, the mixed venous pH fell from 7.36 at rest to 7.30 at LAT and to 7.13 at Max. Thus, as work rate increases above the LAT, changes in pH, reflecting changes in buffer base, account for the major changes in the PCO(2)-CCO(2) relationship, causing Cv(CO(2)) to decrease, despite increasing mixed venous PCO(2). Furthermore, whereas the increase in the arteriovenous CCO(2) difference of 2.2 mM below LAT is mainly due to the increase in Cv(CO(2)), the further increase in the arteriovenous CCO(2) difference of 4.6 mM above LAT is due to a striking fall in arterial CCO(2) from 21.4 to 15.2 mM. We conclude that changes in buffer base and pH dominate the PCO(2)-CCO(2) relationship during exercise, with changes in Hb and blood oxyhemoglobin saturation exerting much less influence.

Adult↗

A noninvasive assessment of pulmonary perfusion abnormality in patients with primary pulmonary hypertension.

STUDY OBJECTIVES: The ventilatory equivalent for CO(2) (ie, the ratio of minute ventilation [VE] to carbon dioxide output [VCO(2)]) is increased in patients with primary pulmonary hypertension (PPH) consequent to an increase in physiologic dead space and alveolar ventilation. We wished to see whether the VE/V(2) ratio correlated with the abnormality in pulmonary hemodynamics in PPH patients and whether it changed in response to prostacyclin infusion. METHODS: Following right-sided heart catheterization, 10 patients with severe PPH were studied in the coronary-care unit while hemodynamic and gas exchange measurements were measured simultaneously before and after infusion with epoprostenol (Epo), a prostacyclin analog. Studies were performed at baseline and during IV infusion of two to three increasing dosages of Epo in 10 PPH patients (NYHA class III-IV). Four patients had radial artery catheters for simultaneous blood gas measurements. Nine healthy subjects who were matched by sex, height, and weight underwent gas exchange analyses only. RESULTS: The mean (+/- SD) VE/VCO(2) ratio was higher in PPH patients than in control subjects (50.7 +/- 9.7 vs 30.6 +/- 3.8; p < 0.001). Thirteen measurements made in four patients showed that the VE/VCO(2) ratio correlated with the physiologic dead space/tidal volume ratio (r = 0.78; p = 0.002). The VE/VCO(2) ratio measurement at baseline correlated significantly with total pulmonary vascular resistance (TPVR) (r = 0.70; p = 0.02) but not with mean pulmonary artery pressure (mPAP) or cardiac index. During Epo infusion, the VE/VCO(2) ratio decreased with increasing dosage in 6 of 10 patients, with no change or slight increases in the 4 remaining patients. Considering all doses, the VE/VCO(2) ratio decreased significantly in response to the short-term administration of Epo. The decrease tended to parallel the pattern of decrease in TPVR, but the changes in both variables were too small to provide a statistically significant correlation. The mPAP did not change significantly in response to Epo infusion, although TPVR did change at the highest dosage. CONCLUSIONS: In patients with severe PPH, the VE/VCO(2) ratio correlated significantly with TPVR but not with mPAP or cardiac index. The VE/VCO(2) ratio decreased systematically from baseline with the dose of Epo in some but not all patients. The VE/VCO(2) ratio and TPVR decreased significantly in response to Epo when all doses were considered. Further studies are needed to elucidate whether noninvasive gas exchange measurements may be clinically useful in the evaluation of the severity of pulmonary vascular disease and the effectiveness of pulmonary vasodilator therapy.

Cardiac Catheterization↗

[Effect of dingxin recipe on intracellular free calcium, membrane potential and mitochondria membrane potential in normal and hypoxia myocytes of rats].

OBJECTIVE: To elucidate the molecular mechanism on anti-arrhythmic function of Dingxin Recipe (DXR). METHODS: Cardial myocytes isolated by trypsin method were cultured and labelled with various fluorescence stains. DXR contained serum induced changes of cytolic calcium concentration [Ca2+]i, cell membrane potential (MP) and mitochondria membrane potential (MMP) were determined with laser confocal microscopy. RESULTS: Hypoxia caused increase of [Ca2+]i and MMP, and decrease of MP, while DXR contained serum lowered the [Ca2+]i in normal or hypoxian myocytes, improved hypoxia induced MP reduction and maintain MMP at baseline level under hypoxia circumstances. CONCLUSION: Through inhibiting the hypoxia caused [Ca2+]i and MMP elevation and MP lowering, DXR displays its action in protecting myocardial cells to prevent and treat arrhythmia.

Animals↗

Comparison of exercise cardiac output by the Fick principle using oxygen and carbon dioxide.

BACKGROUND AND STUDY OBJECTIVE: Theoretically, cardiac output (CO) calculated by the Fick principle should be the same using O(2) (CO[O2]) or CO2 (CO[CO2]) as the test gas. However, agreement depends on the accuracy of gas exchange and blood gas measurements and the validity of the equations to convert measured variables into blood gas contents. Considering the widespread use of indirect estimates of pulmonary artery blood PCO2 and CO2 content to measure Fick principle CO during exercise, we wished to determine whether CO[O2] and CO[CO2] were equal during exercise and whether CO[CO2] could be accurately and precisely determined using direct measures of pulmonary artery blood. PREPARATION AND METHODS: Five healthy young nonsmoking volunteer men performed incremental exercise from rest to peak exercise on two separate occasions with intervening rest. Catheters were placed in brachial and pulmonary arteries to allow repeated blood sampling every minute during concurrent breath-by-breath gas exchange measurements from rest to peak exercise. CO[O2] was compared with CO[CO2] at multiple levels of exercise. Using standard equations, arterial and mixed venous O2 contents were calculated from hemoglobin concentration (Hb), oxyhemoglobin saturation (SO2), and PO2, whereas CO2 contents were calculated from PCO2, pH, Hb, and SO2. Blood gas analyzers were used for measurement of pH, PCO2, and PO2, and a co-oximeter was used for measurement of Hb and SO2. Initial calculations suggested that exercise CO[CO2] was 14% higher than CO[O2] and helped disclose small systematic measurement errors in PCO(2) for values > 45 mm Hg detected by proficiency testing surveys and documented with blood tonometry in the blood gas analyzer. RESULTS: After correcting PCO2 for the small systematic measurement error found, the measures and equations used to calculate arterial and mixed venous O2 and CO2 contents were adequate to provide mean CO values that are reasonably similar. However CO[CO2] values were more than twice as variable as CO[O2]. CONCLUSIONS: The increased variability of Fick principle CO[CO2] compared with CO[O2] is attributable to the much lower extraction ratio for CO2 and the greater complexity in calculation of blood CO2 than O2 contents. These results raise concerns about the accuracy and precision of estimating CO and stroke volume using CO2 as a test gas, even with direct measurement of blood CO2 contents in normal subjects.

Adult↗

Spectroscopic comparison of different DNA structures formed by oligonucleotides.

Six different nucleic acid structures including duplex, triplex and quadruplex are formed by oligonucleotides. Their structural properties are studied in detail by four spectroscopic techniques, i.e. CD, UV, NMR and fluorescence. Results are: CD Spectra: The common characteristics is a negative band at 240 nm, and the spectra are different from each other in the range 260-300 nm. Many factors such as chain direction, sugar puckering, orientation of the glycosyl bond, base stacking and sequence can effect their conformation and then show diversity and complexity in the spectra. UV Spectra: The UV spectra of all forms are quite similar, all of them exhibit a sharp positive peak around 210 nm and a broad positive band in the region of 240-280 nm. Although the bands are different in absorbance, the spectra are not characteristic enough to distinguish these forms. In addition, their thermal denaturation is also observed by UV spectrum, different melting curves and points are shown and some thermodynamic information is provided. NMR Spectra: Since the G residues in the six samples all participate in hydrogen bond, the imino proton can not exchange with the solvent freely so as to allow an observable resonance to arise. The resonance number and chemical shift will vary with the change in base-pairing number and mode as well as the whole geometry of its molecule. Fluorescence Spectra: The interaction mechanisms between EB and these structures are different. B type duplex and triplex adopt an intercalative mode in which the efficiency of energy transfer is relatively high and the fluorescence of EB can not be quenched easily. While for the parallel duplex, outside binding is predominant in which energy transfer can hardly happen and most of its fluorescence can be quenched. As for the quadruplex, groove binding is possible, so the efficiency of energy transfer is higher than that in outside binding, but lower than that in intercalative binding, and fluorescence is quenched partly.

Circular Dichroism↗

Aerobically generated CO(2) stored during early exercise.

Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine.

Adult↗

Overexpression of protein kinase Calpha in MCF-10A human breast cells engenders dramatic alterations in morphology, proliferation, and motility.

A nonmetastatic human mammary epithelial cell line (MCF-10A) was engineered to overproduce protein kinase Calpha (PKCalpha) so as to investigate a role for this isoform in the metastatic phenotype. PKCalpha transfectants (clone 26alpha) expressed an 8-fold higher level of PKCalpha protein without compensatory alterations in other isoforms. Clone 26alpha proliferated slowly (accumulating in G1 of the cell cycle) but exhibited pronounced increases in motility and adhesion. Elevated expression of cell cycle inhibitor p27 and focal adhesion proteins was observed, whereas E-cadherin expression decreased to undetectable levels. These observations were consistent with the morphology of PKCalpha transfectants (large, disaggregated, and flat, with lamellipodia and extensive actin fibers) and control cells (small, aggregated, and refractile). Treatment with PKC inhibitors or transfection of a dominant negative (dn) mutant of Rac1, but neither dn RhoA nor dn cdc42, reduced the motility of clone 26alpha, implicating PKCalpha catalytic activity and endogenous Rac1, respectively, in the PKCalpha-induced phenotype. Overall, PKCalpha overexpression suppresses proliferation while endowing MCF-10A cells with properties consistent with the metastatic phenotype.

Breast↗

Photoinduced inactivation of protein kinase C by dequalinium identifies the RACK-1-binding domain as a recognition site.

1,1'-Decamethylenebis-4-aminoquinaldinium diiodide (DECA; dequalinium) is an anti-tumor agent and protein kinase C (PKC) inhibitor whose mechanism of action with PKC is unknown. This study reports that with human PKC alpha, DECA exhibited competitive inhibition (Ki = 11.5 +/- 5 microM) with respect to RACK-1 (receptor for activated C kinase-1), an adaptor protein that has been proposed to bind activated PKC following translocation (Ron, D., Luo, J., and Mochly-Rosen, D. (1995) J. Biol. Chem. 270, 24180-24187). When exposed to UV light, DECA covalently modified and irreversibly inhibited PKC (alpha or beta), with IC50 = 7-18 microM. UV/DECA treatment of synthetic peptides modeled after the RACK-1-binding site in the C2 region of PKC beta induced modification of Ser218-Leu-Asn-Pro-Glu-Trp-Asn-Glu-Thr226, but not of a control peptide. This modification occurred at a tryptophan residue (Trp223) that is conserved in all conventional PKC isoforms. In overlay assays with native RACK-1 that had been immobilized on nitrocellulose, UV-treated control PKC alpha bound well to RACK-1, whereas UV/DECA-inactivated PKC alpha had reduced binding activity. The significance of these findings is shown with adenocarcinoma cells, which, when pretreated with 10 microM DECA and UV light, exhibited diminished 12-O-tetradecanoylphorbol-13-acetate-induced PKC alpha translocation. Overall, this work identifies DECA as a tool that prevents PKC translocation by inhibiting formation of the PKC.RACK-1 complex.

Amino Acid Sequence↗

Deletion analysis of protein kinase Calpha reveals a novel regulatory segment.

Using a combined pharmacological and genetic approach, we have identified aa 260-280 in the C2 region as a critical factor in the catalytic function of protein kinase Calpha (PKCalpha). Progressive truncations from the N-terminus as well as selected internal deletion mutants were expressed in Saccharomyces cerevisiae and tested for altered sensitivity to dequalinium, a PKC inhibitor whose target site was previously mapped to the catalytic domain. PKC mutants representing truncations of up to 158 amino acid residues (aa) from the N-terminus (ND84 and ND158) displayed 60-63% inhibition of kinase activity by 50 microM dequalinium, somewhat more sensitive than the wild-type PKCalpha enzyme (45% inhibition). Mutant ND262, lacking N-terminal aa 1-262, was inhibited by almost 72% with 50 microM dequalinium, but mutant ND278, which lacked an additional 16 aa, was inhibited by only 9% of total activity. This result suggests that a C-terminal segment of the C2 region (aa 263-278) influences inhibition by dequalinium at low micromolar concentrations. An internal deletion mutant (D260-280) which retains the entire primary structure of PKCalpha except for aa 260-280, was similarly inhibited by only 4% with 50 microM dequalinium. In the absence of dequalinium and despite the presence of a nearly complete regulatory domain, this mutant exhibited constitutive activity (both in vitro and in a phenotypic assay with S. cerevisiae) that could not be further stimulated even by the potent activator TPA. Taken together, our findings suggest that, in the native structure of PKCalpha, the segment described by aa 260-280 regulates PKCalpha activity and influences the sensitivity of PKCalpha to dequalinium.

Animals↗

Formation and characteristics of an unusual lambda-DNA species.

An unusual DNA species, termed as DNA species A, has been isolated and purified from thermal-denatured lambda-DNA Hind III by Sephadex G-200 gel filtration. Our studies indicate that DNA species A is resistant to DNase I digestion and has a higher melting point. The new DNA species showed a lower absorbency at 260 nm, and a lower fluorescence quantum yield after interaction with ethidium bromide (EB) than native double-stranded lambda-DNA. CD spectrum of DNA species A consists of a broad positive band centered at 245 nm and a weak negative band at 220 nm. transmission electron microscope (TEM) visualizations showed that their lengths of DNA species A fell mainly in three regions (300-500 nm, 750-1000 nm and 1500 nm) that corresponded to three fluorescence bands in the EB-stained gels. Their apparent width and height were 65-75 nm and 2.2 nm respectively as observed by images of atomic force microscope (AFM).

Circular Dichroism↗

[Intrasplenic metastasis of malignant ovarian tumor: clinical analysis of 12 cases].

Intrasplenic metastasis of ovarian malignancies are uncommon. From 1986 to 1992 only 12 such cases were diagnosed, being 1.2% of the total number of patients with ovarian malignancies treated in tumor hospital during the same period. Of the 12 metastasis, 6 were poorly differentiated. Diagnosis was made through imaging techniques or surgery. The median interval from the diagnosis of the primary disease to intrasplenic involvement was 28 months. The metastatic lesions, presented themselves as single or multiple nodes within the cortex of the spleen. Clinical features were not remarkable. It was thought that the occurrence of intrasplenic involvement might be due to greater tumor bulk, poor differentiation and decreased host immuno-competence caused by chemotherapy. Most of the intrasplenic metastasis was found after liver metastasis or simultaneously with the latter. The main route of the tumor spread might be via blood vessels. Sole intrasplenic metastasis can be treated by surgery with a temporarily good result. Poor prognosis and high mortality characterize intrasplenic metastasis. The median survival was only 7 months.

Adult↗

[Determination of esculetin in semen Euphorbiae lathyridis L. by TLCS and comparison on the quality in different areas].

A TLC-densitometric method for the determination of oesculetin in Semen Euphorbia lathyridis (Euphorbiae lathyrdis) was established, and esculetin content in Semen Euphorbia lathyridis from three different producing areas (Zhengzhou, Chengdu and Chongqing) was determined. The method is accurate, sensitive and simple. The recovery is 98.63% and the coefficient of variation is 1.59% (n = 5). The esculetin average contents in the three samples are 0.3013%, 0.2046% and 0.2094% respectively.

China↗

Coronary artery stenoses: a phantom study using contrast enhanced three-dimensional electron beam tomography.

This paper evaluated the accuracy of electron beam tomographic angiography (EBA) with conventional coronary arteriography (CCA) using four graded artificial stenoses in a postmortem swine coronary phantom model. The sensitivity, specificity, and accuracy of EBA for diagnosing significant stenosis (> or =50% stenosis) were 94.3%, 96.7%, and 95.8%, respectively. The diagnostic accuracy of EBA had no significant difference with CCA (chi(2)=0.0162; P>.05). EBA three-dimensional (3D) procedures had high interobserver reproducibility (k=.92-.95, P>.05). Maximum intensity projection (MIP) was the most sensitive and curved planar reformation (CPR) was the most accurate 3D procedure for quantitatively identifying coronary stenosis. EBA yields promising results concerning the visualization of coronary artery stenosis with high accuracy for stenoses >50%.

Animals↗

The usefulness of technetium-99m-MIBI scintimammography in diagnosis of breast cancer: using surgical histopathologic diagnosis as the gold standard.

UNLABELLED: The purpose of this study was to evaluate the usefulness of 99mTc-MIBI scintinammography for the detection of breast cancer. METHODS: Sixty-one consecutive patients referred for a suspicions breast lesion on clinical examination were studied with 99mTc-MIBI scintimammography. There were 60 female patients and 1 male patient with 63 pulpable breast abnormalities. Each patient received 20mCi 99mTc-MIBI intravenously. Ten and 120 minutes postinjection, three planar views, right and left lateral prone and anterior supine thoracic views, were obtained. The patient underwent surgery within one week and the final diagnostic results (histopathology) were obtained. RESULTS: Thirty-two of 63 abnormalities of breast were pathologically confirmed breast cancer, and 31 were benign lesions. In the group of patients studied, the sensitivity of 99mTc-MIBI scintimammography was 78.1% (25 true-positive, 7 false-negative) and the specificity was 90.3% (28 true-negative, 3 false positive). The positive predictive value was 89.3%, the negative predictive value was 80.0%, the positive likelihood ratio was 8.1, the negative likelihood ratio was 0.2. CONCLUSION: This study showed the high diagnostic accuracy of 99mTc-MIBI scintimammography in detecting breast cancer. 99mTc-MIBI scintimammography can be used as an assistant method to non-invasively assess breast cancer invasiveness before surgery.

Breast Diseases↗